Organophosphorus reagents. A practical approach in chemistry

274 Pages·2004·3.3 MB·English

by  Patrick J. Murphy

Contents
List of contributors xi
1. Organophosphorus chemistry 1
PatrickJ.Murphy
1. Introduction 1
2. Nomenclature 1
3. Practicalmethods 2
References 12
2. The synthesis and applications
of phosphines 15
MatthewL.ClarkeandJonathanM.J.Williams
1. Introduction 15
2. Preparationoftertiaryphosphines 18
3. Preparationandreactivityofprimaryandsecondaryphosphines 26
4. Polydentatephosphinesandmacrocycles 32
5. Chiralphosphines 35
6. Synthesisandapplicationsofphosphinesinenvironmentally
benigncatalysis 42
7. Applicationsofphosphinesincatalysis 45
References 48
3. Applications of phosphorus (III) and (V)
compounds as reagents in synthesis 51
R.AlanAitkenandNaziraKarodia
1. Introduction 51
2. Deoxygenationanddesulfurizationreactions 51
3. Halogenationreactions 63
4. Dehydrativecouplingandcyclizationreactions 74
5. Sulfurizationreactions 81
6. Miscellaneousreactions 87
References 95
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Contents
4. The Wittig and related reactions 99
AndrewD.AbellandMichaelK.Edmonds
1. Introduction 99
2. Standardreagentsandprocedures 104
3. Modificationstothestandardreagentsandprocedures 111
4. Roleinsynthesis 116
References 126
5. Applications of the Wittig reaction in
the synthesis of heterocyclic and
carbocyclic compounds 129
RainerSchobert
1. Introduction 129
2. Ring-closurevariantsutilizinghighlyreactive
ω-carbonyl-ylides 131
3. Ring-closurevariantsemployinglessreactiveω-carbonylylidesor
‘non-classical’Wittigolefinationsofestersandamides 137
References 148
6. Preparation and reactions of
iminophosphoranes and their synthetic
applications in the aza-Wittig reaction 151
J.MikeSouthernandIanA.O’Neil
1. Introduction 151
2. Preparationofiminophosphoranes 152
3. Removaloftriphenylphosphineoxide 154
References 168
7. Phospho-transfer processes leading to
−−
[P C] bond formation 171
MatthewD.Fletcher
1. Introduction 171
2. TheMichaelis–Arbuzovreaction 172
3. TheMichaelis–Beckerreaction 185
4. ThePerkowreaction 191
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Contents
5. TheAbramovreaction 194
6. ThePudovikreaction 198
7. TheKabachnik–Fieldsreaction 204
8. Conjugateadditionsofphosphorus(III)reagents 208
References 210
8. Low-coordinated phosphorus compounds 215
SvenAsmus,UweBergsträßer,HeinrichHeydt,
MarionSchmitzandManfredRegitz
1. Introduction 215
2. Phosphoruscompoundshavingcoordinationnumber1 217
3. Phosphoruscompoundshavingcoordinationnumber2 223
References 233
9. Phosphorus methods in
nucleotide chemistry 237
DavidM.WilliamsandVickiH.Harris
1. Introduction 237
2. Outlineofchemistry 237
3. Synthesis 241
4. Analysisandpurification 264
Acknowledgements 271
References 271
Index 273
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1
Organophosphorus chemistry
PATRICK J. MURPHY
1. Introduction
The impact of organophosphorus chemistry on modern synthetic chemistry is
difficult to quantify, but one can safely assume that the study of this element
has influenced all areas of chemical endeavour.1 Organophosphorus chemistry,
−−
as a discrete area of study, is the study of compounds containing a C P bond
and this book is largely focused on this topic. However, other areas of interest
includingazaphosphorus, oxyphosphorusandmetallophosphoruschemistryare
discussedeitherexplicitlyastopicsorinanimplicitmannerwithinthechemistry
detailed in each chapter. The purpose of this introductory chapter is to cover
many of the general aspects of organophosphorus chemistry and the chemical
techniquesrequiredfortheirpreparation,includingpracticalmethodscommonly
encounteredandsomeaspectsofspectroscopy.
Manytextsonorganophosphoruschemistryhavebeenpublishedrangingfrom
in-depthstudiesofthesubjectasawhole1,2tomoregeneraltexts,3whichwould
serveasageneralintroductiontothefield.Ofthemorecomprehensivetexts,the
four-volume2a–dseriesentitledTheChemistryofOrganophosphorusCompounds
edited by Hartley provides core material published before 1990 and represents
an excellent starting point for those new to the field. A considerable amount
of organophosphorus chemistry is published in the core literature, which can
be difficult to access, however, the periodical Organophosphorus Chemistry4
publishedannuallybytheRoyalSocietyofChemistryoffersayearlyreviewof
thehighlightsandkeydevelopmentsinthefield.4Severalotherperiodicals,which
are no longer published are worthy of note5 and the two journals Phosphorus,
SulfurandSilicon,andtheRelatedElementsandHeteroatomChemistryprovide
aconsiderablequantityofusefulinformationfortheseriousresearcher.6
2. Nomenclature
Thenomenclatureofphosphorus-containingcompoundsiscomplicatedtosome
extent by the overlap of inorganic and organic nomenclature, particularly with
−− −−
respect to compounds containing the P O H functionality. From the point of
view of this volume, the basic nomenclature used for trisubstituted phosphorus
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P.J.Murphy
compounds is given in Scheme 1, and that for tetrasubstituted compounds is
showninScheme2.1
OR
R
Phosphines; R = H, alkyl, aryl Phosphonites;
P
P R = Hal R = H, alkyl, aryl
RO R
R R
OR OR
Phosphinites; Phosphites;
P P
R = H, alkyl, aryl R = H, alkyl, aryl
R R RO OR
Scheme1 Nomenclaturefortrisubstitutedphosphoruscompounds.
R
P+ R Phosphonium salts; OR
R = alkyl, aryl
R R
R Phosphinates;
P
R = alkyl, aryl
R O R
R Alkyene phosphoranes (ylides);
P OR
R = alkyl, aryl
R C R
2
OR Phosphonates;
P
R = alkyl, aryl
O R
R
R Azaphosphenes;
P OR
R = alkyl, aryl
RN R
OR Phosphates;
P
R = alkyl, aryl
R O OR
R Phosphine oxides; R = alkyl, aryl
P
Phosphoryl halides; R = Hal
O R
Scheme2 Nomenclaturefortetrasubstitutedphosphoruscompounds.
3. Practical methods
The reader is referred to more general texts for further information on general
experimental techniques.7 However, it is hoped that for those not experienced
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1:Organophosphoruschemistry
withorganicchemistry,enoughinformationhasbeenprovidedheretoperformthe
experiments.Thischapterisintendedtofamiliarizethereaderwiththeequipment
andtechniques,whichareusedintheprotocolsthroughoutthebook.
3.1 Solvents
Aswithmostsyntheticorganicchemistry, theavailabilityofpure, andinmany
cases,dryandoxygen-freesolventsisessentialforbotheffectingsynthetictrans-
formations and for purification purposes. Awide range of organic solvents are
employedinorganophosphoruschemistry,andmanyareavailablefromsuppliers
inananhydrousform,packagedundernitrogeninSureSeal™ bottles,whichare
usually suitable for use in the reactions we will cover. However, an alternative
methodistopurchasetechnical-gradesolvents,whicharethentreatedwithchem-
icaldryingagentstoremovethemoisturepresentandthendistilled,eitherdirectly
beforeuseorontoadryingagentforstorage,suchasmolecularsieves.Arangeof
methodsareavailablefordryingsolvents8–10andthetypicalsolventsemployedin
organophosphoruschemistryandtheirmethodofdistillationaredetailedbelow.
3.1.1Diethyletherandtetrahydrofuran(THF)
Thesesolventscanbedriedefficientlybyfirstdryingoversodiumwireandthen
distilling directly before use, from sodium metal under an inert atmosphere in
the presence of a small amount of benzophenone. This combination produces
adeep-blue/purplesolutionofsodiumbenzophenoneketylifthesolventisdry,
and the ketyl colour acts as an indicator, which, when it fades, indicates that
additional sodium is needed. This is also an advantageous method as the ketyl
is an extremely efficient oxygen scavenger.8 It is important that peroxide-free
diethyl ether and tetrahydrofuran (THF) are employed in the still, and it is also
importanttoensurethatperoxidesdonotaccumulateinstoredsamplesofthese
solvents.Asimpletestforthisistomixasampleofthesolvent(approximately
1mL)withglacialaceticacid(1mL)containingKIcrystals(100mg).Ayellow
colourationindicatesthepresenceofasmallquantityofperoxides,whilstadeep
brown colouration indicates a higher concentration. Peroxides can be removed
in a number of ways,8,9 the most convenient being to wash repeatedly with an
acidifiedFeSO solution(FeSO (60g),concentratedH SO (6mL),andwater
4 4 2 4
(110 mL)), until a negative peroxide test is obtained. The solvent should then
bewashedwithKMnO solution(0.5%), NaOHsolution(5%), water, andthen
4
driedoverCaCl for24h.
2
3.1.2Benzeneandtoluene
These solvents are most conveniently dried by treatment with calcium hydride
followedbydistillationonto4Åmolecularsieves.
3.1.3Petroleumether(petrol)
Petroleumethercanbedriedbydistillationontoactivated4Åmolecularsieves.
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P.J.Murphy
3.1.4Dichloromethane
Dichloromethanecanbedriedbytreatmentwithcalciumhydrideinacontinuous
stillorcanbestoredbydistillationonto4Åmolecularsieves. Caution! Never
treatchlorinatedsolventswithsodiumorstrongbases—anexplosionmayoccur.
3.1.5Dimethylformamide(DMF)
Stirovercalciumhydrideorphosphoruspentoxidefor24h,filterunderaninert
◦
atmosphereanddistil(56 Cat20mmHg)onto3Åmolecularsieves.Analtern-
ative method is to dry over three batches of 3 Å molecular sieves (5% w/v,
3×12h).
3.1.6Molecularsieves
The immediate use of dried, deoxygenated solvents is recommended, although
non-etherealsolventscanbestoredoveractivatedmolecularsievesinthoroughly
dried containers under N /Ar. It is recommended that new molecular sieves be
2
◦
dried before use by heating them in a well-ventilated oven at 320 C for 3 h
followed by cooling them in an evacuated desiccator, which is filled with dry
N /Ar.Sievesmaybereusediftheyarefreefromresidualsolvents.
2
3.1.7Distillationset-up
If regular amounts of solvent are required, it is convenient to set up a solvent
distillation apparatus, commonly referred to as a solvent still. A solvent still
enablesacontinuoussupplyofdrysolventtobeavailable,whichcanbeconveni-
ently collected under an inert atmosphere. Common stills are those for drying
diethyl ether, THF, and dichloromethane. The still shown in Figure 1.1 has an
adaptationforremovingsolventsfromthestill-headcollectionreservoirthrough
aseptumcapbysyringeor, iflargerquantitiesarerequired, aflaskcanbecon-
nected to the Quickfit adapter on the still-head. These two methods minimize
the exposure of the solvent to the atmosphere. When using a solvent still, the
followingprecautionsshouldbeobserved:
1. Thestillshouldbesituatedinanefficientfumehood,andalltubingforinert
gasandwatersuppliesshouldbesecurelyattachedusingcopperwireorplastic
cableties.
2. Theheatingmantleshouldbeofsuchadesignthatthereisnoriskofsparks
igniting the solvent. This also applies to all electric cables and plugs. The
mantle should also incorporate an electricity cut-out device to operate if the
watersupplytothecondenserfails.
3. It is imperative that the bottom flask containing the drying agent should not
be allowed to boil dry. This risk can be minimized if the flask is of greater
capacitythanthecollectionreservoirandisregularlytoppedupwithsolvent.
4. Duringcooling,anadequateflowofinertgasshouldbemaintained.
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1:Organophosphoruschemistry
Inert gas supply
Two-way tap
Water
Condenser
Water
Septum
Two-way tap
Overflow device
Three-way tap
To receiving flask
Stoppered side-arm
with retaining clip
(to refill still) Round-bottomed flask
Fig.1.1 Generalset-upforasolventstill(reproducedwithpermissionfromRef.13).
5. Caution! The use of a semi-permanent still for ethereal solvents can lead
to a build-up of peroxides. The solvent should be checked for peroxides at
frequentintervals,andifthesearedetected,thestillshouldbedismantledand
thedryingagentandperoxidescarefullydestroyed.Also,whenrenewingthe
still,freshbatchesofthesolventanddryingagentshouldbeused.
3.2 Working under an inert atmosphere
Manypreparationsrequiretheuseofaninertatmosphereandarethuscarriedout
under an atmosphere of anhydrous nitrogen or argon.Argon has the advantage
ofbeingheavierthanairand,therefore,providesamoreeffectivebarrieragainst
theoutsideatmosphere,butnitrogenismorecommonlyusedowingtoitslower
cost.Thebestmethodforensuringthatreactionsarepurgedfreeofoxygenisto
employ a purpose-built double manifold of the type shown in Figure 1.2. This
apparatus provides the inert gas and a vacuum source via two-way stopcocks
andallowsseveralinertatmosphereexperimentstoberunsimultaneously.Itcan
alsobefittedwithaQuickfitadapterfittedwithaseptum,whichcanbeusedfor
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P.J.Murphy
Connector
Two-way stopcock
Inert gas supply
To vacuum
To apparatus
Paraffin oil
Fig.1.2 Doublemanifoldapparatus(reproducedwithpermissionfromRef.13).
purgingsyringeswithinertgas.Thesupplyofinertgastothemanifoldshouldbe
controlledintwostagesusingacylinderregulatorandthenaneedlevalve, and
theapparatusshouldalsobeequippedwithabubblertocontrolthereleaseofgas.
Further examples of apparatus designed for specific applications appear in
therecommendedexperimentaltextsfororganicsynthesis.7
3.3 Reaction apparatus
Avarietyofexperimentalset-upswillbeemployedthroughoutthisbook.Incases
where cooling of a process is required, an arrangement of glassware similar to
that shown in Figure 1.3 will be suitable. This consists of a three-necked flask
equippedwithamagneticstirringbar,aseptum,alowtemperaturethermometer,
andaninletforinertgasandvacuum.Liquidreagentsandsolventscanbeadded
viasyringethroughtheseptumand, providedthatanadequateflowofinertgas
ismaintained,theseptumcanberemovedtoallowtheadditionofsolids.
Ifheatingofthereactionisrequired,theflaskshouldbeequippedwithareflux
condenserandanefficientheatingapparatus.Twooptionsaregenerallyavailable
forheatingareaction,first,anisomantlewhichoffersdirectheatingtotheflask
andcanbeequippedwithastirringmechanism.Alternatively,anoil-bathismore
frequently used as illustrated (Figure 1.4) as this option offers more controlled
heating. Itisrecommendedthatonlyfreshparaffinorsiliconeoilisusedinthe
bathandthatatemperatureregulatingdeviceisfittedtothebathinconjunction
withawatercut-outmechanism.
3.4 Standardization of organolithium reagents
Inmanyofthepreparationsdetailedinthisbook,theuseofn-BuLiisrequired.
It is recommended that for any purchased solution, this reagent is standardized
before use as there is generally a considerable difference between the expected
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